Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of Susceptibility to Cirrhosis Associated with Alcohol Abuse

Autor: Rodrigo M. Florentino, Antônio Carlos Melo Lima Filho, Kemper Nunes dos Santos, Igor Brasil Costa, Matheus de Castro Fonseca, Paula Vieira Teixeira Vidigal, Marcone Loiola dos Santos, Andressa França, Michael H. Nathanson, Dabny Goulart Missiaggia, Fernanda O. Lemos, M. Fatima Leite
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Alcoholic liver disease
Cirrhosis
endocrine system diseases
NFE2L2 gene
Gene Expression
Cirrose Hep?tica / patologia
Hepacivirus
lcsh:Chemistry
0302 clinical medicine
Liver Cirrhosis
Alcoholic
Medicine
Promoter Regions
Genetic
lcsh:QH301-705.5
Spectroscopy
General Medicine
Middle Aged
Hepatitis C
Computer Science Applications
Liver
030220 oncology & carcinogenesis
030211 gastroenterology & hepatology
Female
Adult
endocrine system
congenital
hereditary
and neonatal diseases and abnormalities
NF-E2-Related Factor 2
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
Catalysis
Article
Nrf2
Fator 2 Relacionado a NF-E2 / gen?tica
Inorganic Chemistry
03 medical and health sciences
Marcadores Gen?ticos
SNP
Humans
Genetic Predisposition to Disease
Physical and Theoretical Chemistry
Polymorphism
Molecular Biology
Gene
F?gado / anatomia & histologia
Ethanol
Polimorfismo Gen?tico / imunologia
business.industry
Organic Chemistry
nutritional and metabolic diseases
Promoter
medicine.disease
NFE2L2
Liver Transplantation
Oxidative Stress
Alcoolismo / diagn?stico
lcsh:Biology (General)
lcsh:QD1-999
Genes / imunologia
Genetic marker
Case-Control Studies
Cancer research
business
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 14, p 3589 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 14
Repositório Digital do Instituto Evandro Chagas (Patuá)
Instituto Evandro Chagas (IEC)
instacron:IEC
ISSN: 1422-0067
Popis: Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin &
eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje